The ability to accurately and reproducibly produce particles having a well defined particle size and particle size distribution from a liquid feed stock has application in a variety of fields, including food, chemicals, and pharmaceuticals. Such control of particle size and particle size distribution is particularly important in pharmaceutical applications where liquid or dry powder particles containing an active agent are administered to a patient. Controlling the particle size and particle size distribution is desirable in such applications in order to achieve delivery of such particles in a known and repeatable manner.
Powders for pharmaceutical drug administration have been made by spray drying. Spray drying is a conventional chemical processing unit operation used in the chemical, food, and pharmaceutical industries to produce dry particulate solids from a variety of liquid and slurry materials. The process involves rapidly transforming a liquid feed into a dried particulate form by atomizing the feed into a hot drying medium.
Conventional spray drying systems and processes have been disclosed. For example, U.S. Pat. Nos. 5,260,306, 4,590,206, GB 2,105,189, and EP 072 046 describe a method for spray drying nedocromil sodium to form small particles preferably in the range from 2-15 mm for pulmonary delivery. U.S. Pat. No. 5,376,386 describes the preparation of particulate polysaccharide carriers for pulmonary drug delivery, where the carriers comprise particles sized from 5-100 mm and having a rugosity of less than 1.75. WO 96/09814 discloses spray-dried smooth and spherical microparticles which either carry a therapeutic or diagnostic agent. U.S. Pat. No. 6,022,525 discloses microcapsules prepared by spray-drying and which are useful for ultrasonic imaging. Additionally, aerodynamically light particles for pulmonary delivery and particles incorporating surfactants for pulmonary drug delivery and their preparation are disclosed in U.S. Pat. Nos. 5,855,913 and 5,874,064. The spray drying of hydrophobic drugs and excipients is disclosed in U.S. Pat. Nos. 5,976,574, 5,985,248, 6,001,336, and 6,077,543. U.S. Provisional Patent Application 60/222,067 filed on Aug. 1, 2000 discloses a spray drying process that can be tailored to produce substantially monodisperse particles or multimodal particles having well defined and controllable particle size distributions. Additional spray drying processes are disclosed in EP 1004349, WO 96/32149, WO 99/16419, and U.S. Pat. Nos. 6,000,241, and 6,051,256, and in The Spray Drying Handbook, K. Masters. All of the aforementioned references are incorporated herein by reference in their entireties. Various atomizers have been used in the spray drying of pharmaceutical powders. These include gas assisted two fluid nozzles, rotary atomizers and ultrasonic atomizers comprising an oscillating horn to create surface instabilities resulting in droplet formation. Examples of each of these various atomizers are disclosed in the patents cited above. Droplet size and droplet size distribution are affected by the selection of the atomizer.
The application of conventional spray drying technology to the field of pulmonary drug administration presents many technical challenges. For example, there are often particular sizing requirements necessary to administer resultant particles to the deep lung. For pulmonary applications, the aerodynamic size of the particles dispersed in an aerosol directly impacts the deposition pattern in the lung. The major factors influencing this final particle size include the initial liquid drop size, the initial solids concentration, and the drying rate. It is advantageous to create small liquid droplets with the highest solids concentration feasible for a particular process to minimize capital equipment and operating costs.
It can be difficult to achieve a desired low moisture content required for physical and chemical stability in the final particulate product, particularly in an economic manner. Finally, it has proven to be difficult to produce the small particles necessary for some pharmaceutical applications, such as pulmonary delivery, in an efficient manner on a large scale suitable for commercial applications.
Therefore, it is desirable to be able to produce spray dried particles in an improved manner. It is further desirable to be able to produce spray dried particles within a narrow size distribution, in particular for pulmonary drug administration. It is further desirable to be able to generate desired particles in an economic manner.